Coronavirus Disease 2019: Clinical Presentation, Pathogenesis and Treatment

A topical collection in Journal of Clinical Medicine (ISSN 2077-0383). This collection belongs to the section "Infectious Diseases".

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Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine, University of Bari “Aldo Moro” Medical School, 70124 Bari, Italy
Interests: clinical immunology; tumor immunology; emergency medicine; pharmacotherapy
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Topical Collection Information

Dear Colleagues,

The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an extraordinary challenge to world’s scientists. High infectivity of the virus, lack of effective antivirals and vaccines, and large asymptomatic populations make the disease hard to conquer. The clinical spectrum of COVID-19 appears to be abnormally wide, and its pathogenesis is yet to be decoded. Patients can experience a range of clinical manifestations, from no symptoms to critical illness. Accurate prediction of clinical outcomes for patients across this spectrum is often difficult. Advanced age and comorbidities are associated with more severe disease and poorer outcomes. In severe cases, it seems that most organ damage is done through an immune-mediated mechanism, although SARS-CoV-2 is the necessary initiator. Treatment for COVID‐19 is currently only supportive, focused on appropriate management of the associated respiratory dysfunction. The synergistic role that viral and host-dependent mechanisms play in the disease pathogenesis suggests that new therapeutic strategies must combine antiviral drugs and immune-modulating agents.

This Special Issue is aimed at offering a place to present the state of the art in basic, translational, and clinical research on COVID-19 pathogenesis, diagnosis, and management. Original and review articles dealing with the following issues are welcome:

  • identification of biological and clinical markers that could optimize patient care and resource consumption;
  • immunological profiling of patients;
  • diagnostic value of laboratory tests and imaging techniques;
  • prediction of disease severity and mortality and identification of contributing factors;
  • definition and timing of optimal therapeutic approaches;
  • efficacy, tolerability, and safety of specific therapies.

Prof. Dr. Vito Racanelli
Collection Editor

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Keywords

  • SARS-CoV-2
  • COVID-19
  • pathogenesis
  • clinical presentation
  • diagnosis
  • prognosis
  • therapy

Published Papers (37 papers)

2024

Jump to: 2023, 2022, 2021

10 pages, 494 KiB  
Article
Do Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio Need to Be Stratified for Age and Comorbidities in COVID-19 Disease? A Subgroup Analysis of Two Distinct Cohorts over Disease Course
by Nadya Kagansky, Yochai Levy, Anas Awar, Estela Derazne, Alexander Shilovsky, Dana Kagansky, Victor Chepelev, Evelina Mazurez, Ilia Stambler and Osnat Levtzion-Korach
J. Clin. Med. 2024, 13(2), 605; https://doi.org/10.3390/jcm13020605 - 21 Jan 2024
Viewed by 860
Abstract
Several studies described neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as markers of COVID-19 severity. In a recently published study, age and frailty affected NLR and PLR more than disease severity. The study compared two distinct cohorts. The first comprised older frailer patients [...] Read more.
Several studies described neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as markers of COVID-19 severity. In a recently published study, age and frailty affected NLR and PLR more than disease severity. The study compared two distinct cohorts. The first comprised older frailer patients positive for SARS-CoV-2, with mild or asymptomatic disease, admitted to designated COVID-19 departments in a large geriatric medical center (GMC). The second cohort comprised COVID-19 patients admitted to a large general hospital (GH) for symptomatic disease. This was a follow-up study comparing a subgroup of patients who had NLR and PLR values measured a week after admission. Only 100 of 177 patients in the original GMC cohort had a second NLR test compared to almost all (287 of 289) patients in the general hospital (GH) cohort. The subgroup baseline characteristics did not change significantly from that of the original cohort. Disease symptoms were more prevalent in the GH cohort. In the GMC group, the median second NLR rose from 3.9 to 4.6, while in the GH cohort, the NLR value dropped from 3.5 to 2.8, enhancing the NLR differences between the groups. Smaller changes were observed in the second PLR. These results strengthen the prior results that age and frailty seem to have a stronger impact on NLR and PLR than disease severity. Full article
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13 pages, 847 KiB  
Article
The Effect of Sodium–Glucose Cotransporter-2 Inhibitors on COVID-19 Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study Using the Common Data Model
by Kyoung Ree Lim, Kwang Jin Chun, Bum Sung Kim and Seunghwa Lee
J. Clin. Med. 2024, 13(2), 431; https://doi.org/10.3390/jcm13020431 - 12 Jan 2024
Cited by 1 | Viewed by 759
Abstract
Background: There is no clinical evidence about the effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors on diabetic patients who have been diagnosed with coronavirus disease 19 (COVID-19). Methods: The dataset is based on insurance benefit claims sent to the Health Insurance Review and Assessment [...] Read more.
Background: There is no clinical evidence about the effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors on diabetic patients who have been diagnosed with coronavirus disease 19 (COVID-19). Methods: The dataset is based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea from January, 2018 to April, 2022. Among 9,822,577 patients who were involved in the claims, diabetic patients were divided into two groups based on whether they had a prescription for an SGLT2 inhibitor. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs), which were a composite of all-cause mortality, myocardial infarction, stroke, and revascularization over 90 days. Results: A total of 172,682 patients was analyzed. In the propensity score-matched analysis, the rate of MACCE was lower in the SGLT2 inhibitor group compared to the non-SGLT2 inhibitor group (0.89% vs. 1.31%; hazard ratio, 0.71; 95% confidence interval, 0.53–0.94; p =0.020). Each of the MACCEs showed no differences between the two groups. The rate of pneumonia was similar between the two groups (4.45% vs. 4.39%; hazard ratio, 1.06; 95% confidence interval, 0.91–1.16; p = 0.620). Conclusions: In the diabetic patients who were diagnosed with COVID-19, SGLT2 inhibitors were associated with improved clinical outcomes in terms of MACCEs. SGLT2 inhibitors might be considered for prescription to diabetic patients in the current context of long COVID-19. Full article
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2023

Jump to: 2024, 2022, 2021

11 pages, 1974 KiB  
Systematic Review
Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis
by Yu Jung Choi, Yu Bin Seo, Jun-Won Seo, Jacob Lee, Eliel Nham, Hye Seong, Jin Gu Yoon, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Eun Jung Kim and Joon Young Song
J. Clin. Med. 2023, 12(23), 7375; https://doi.org/10.3390/jcm12237375 - 28 Nov 2023
Cited by 5 | Viewed by 3415
Abstract
Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 [...] Read more.
Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409–0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697–0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals. Full article
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11 pages, 421 KiB  
Article
Analysis of Ischemia-Modified Albumin (IMA) and Coagulation Parameters in Patients with SARS-CoV-2 Pneumonia
by Emel Saglam, Gulsen Sener, Tulin Bayrak, Ahmet Bayrak and Numan Gorgulu
J. Clin. Med. 2023, 12(13), 4304; https://doi.org/10.3390/jcm12134304 - 27 Jun 2023
Cited by 3 | Viewed by 902
Abstract
Background: Coronavirus disease 2019 (COVID-19) is a systemic disease which causes an increased inclination to thrombosis by leading to coagulation system activation and endothelial dysfunction. Our objective in this study is to determine whether ischemia-modified albumin (IMA) can be used as a new [...] Read more.
Background: Coronavirus disease 2019 (COVID-19) is a systemic disease which causes an increased inclination to thrombosis by leading to coagulation system activation and endothelial dysfunction. Our objective in this study is to determine whether ischemia-modified albumin (IMA) can be used as a new marker in patients with COVID-19 for evaluating the increased coagulation risk, pneumonic infiltration, and thus, prognosis. Methods: Our study included 59 patients with COVID-19 compatible pneumonic infiltration on lung computed tomography (CT) who applied to and were hospitalized in the Internal Diseases Outpatient Clinic, then followed up and treated, as well as 29 healthy individuals with a negative COVID-19 rRT-PCR test without any additional disease. Hemogram, coagulation, routine biochemistry, and serum IMA activity parameters were studied. Results: In our study, the higher serum IMA level in COVID-19 patients with pneumonic infiltration compared to that of the healthy control group was found to be statistically significant. No significant correlation was found between the serum IMA levels and the coagulation and inflammation parameters in the 59 COVID-19 patients included. Conclusions: Serum IMA levels in COVID-19 patients with pneumonic infiltration on CT were found to be higher than in the control group. Examination of biochemical parameters, especially thrombotic parameters that affect prognosis such as IMA, can be a guide in estimating pneumonic infiltration. Full article
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20 pages, 3418 KiB  
Review
Unraveling the Underlying Molecular Mechanism of ‘Silent Hypoxia’ in COVID-19 Patients Suggests a Central Role for Angiotensin II Modulation of the AT1R-Hypoxia-Inducible Factor Signaling Pathway
by Christian Albert Devaux and Jean-Christophe Lagier
J. Clin. Med. 2023, 12(6), 2445; https://doi.org/10.3390/jcm12062445 - 22 Mar 2023
Cited by 4 | Viewed by 2613
Abstract
A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules belonging to the [...] Read more.
A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules belonging to the renin angiotensin system (RAS) in COVID-19 patients, we propose a model that explains ‘silent hypoxia’. The RAS imbalance caused by SARS-CoV-2 results in an accumulation of angiotensin 2 (Ang II), which activates the angiotensin 2 type 1 receptor (AT1R) and triggers a harmful cascade of intracellular signals leading to the nuclear translocation of the hypoxia-inducible factor (HIF)-1α. HIF-1α transactivates many genes including the angiotensin-converting enzyme 1 (ACE1), while at the same time, ACE2 is downregulated. A growing number of cells is maintained in a hypoxic condition that is self-sustained by the presence of the virus and the ACE1/ACE2 ratio imbalance. This is associated with a progressive worsening of the patient’s biological parameters including decreased oxygen saturation, without further clinical manifestations. When too many cells activate the Ang II-AT1R-HIF-1α axis, there is a ‘hypoxic spillover’, which marks the tipping point between ‘silent’ and symptomatic hypoxia in the patient. Immediate ventilation is required to prevent the ‘hypoxic spillover’. Full article
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2022

Jump to: 2024, 2023, 2021

21 pages, 1326 KiB  
Review
Omega-3 Polyunsaturated Fatty Acids (n-3 PUFAs) for Immunomodulation in COVID-19 Related Acute Respiratory Distress Syndrome (ARDS)
by Francesca Velotti, Lara Costantini and Nicolò Merendino
J. Clin. Med. 2023, 12(1), 304; https://doi.org/10.3390/jcm12010304 - 30 Dec 2022
Cited by 4 | Viewed by 2641
Abstract
Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), might be complicated by Acute Respiratory Distress Syndrome (ARDS) caused by severe lung damage. It is relevant to find treatments for COVID-19-related ARDS. Currently, DHA and EPA n-3 PUFAs, known for their [...] Read more.
Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), might be complicated by Acute Respiratory Distress Syndrome (ARDS) caused by severe lung damage. It is relevant to find treatments for COVID-19-related ARDS. Currently, DHA and EPA n-3 PUFAs, known for their immunomodulatory activities, have been proposed for COVID-19 management, and clinical trials are ongoing. Here, examining COVID-19-related ARDS immunopathology, we reference in vitro and in vivo studies, indicating n-3 PUFA immunomodulation on lung microenvironment (bronchial and alveolar epithelial cells, macrophages, infiltrating immune cells) and ARDS, potentially affecting immune responses in COVID-19-related ARDS. Concerning in vitro studies, evidence exists of the potential anti-inflammatory activity of DHA on airway epithelial cells and monocytes/macrophages; however, it is necessary to analyze n-3 PUFA immunomodulation using viral experimental models relevant to SARS-CoV-2 infection. Then, although pre-clinical investigations in experimental acute lung injury/ARDS revealed beneficial immunomodulation by n-3 PUFAs when extracellular pathogen infections were used as lung inflammatory models, contradictory results were reported using intracellular viral infections. Finally, clinical trials investigating n-3 PUFA immunomodulation in ARDS are limited, with small samples and contradictory results. In conclusion, further in vitro and in vivo investigations are needed to establish whether n-3 PUFAs may have some therapeutic potential in COVID-19-related ARDS. Full article
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10 pages, 506 KiB  
Article
Prognostic Factors for Pulmonary Fibrosis Following Pneumonia in Patients with COVID-19: A Prospective Study
by Inhan Lee, Joohae Kim, Yohwan Yeo, Ji Yeon Lee, Ina Jeong, Joon-Sung Joh, Gayeon Kim, Bum Sik Chin, Yeonjae Kim, Min-Kyung Kim, Jaehyun Jeon, Yup Yoon, Sung Chan Jin and Junghyun Kim
J. Clin. Med. 2022, 11(19), 5913; https://doi.org/10.3390/jcm11195913 - 7 Oct 2022
Cited by 3 | Viewed by 1771
Abstract
The frequency and clinical manifestation of lung fibrosis accompanied by coronavirus disease (COVID-19) are not well-established. We aimed to identify the factors attributed to post-COVID-19 fibrosis. This single-center prospective study included patients diagnosed with COVID-19 pneumonia from 12 April to 22 October 2021 [...] Read more.
The frequency and clinical manifestation of lung fibrosis accompanied by coronavirus disease (COVID-19) are not well-established. We aimed to identify the factors attributed to post-COVID-19 fibrosis. This single-center prospective study included patients diagnosed with COVID-19 pneumonia from 12 April to 22 October 2021 in the Republic of Korea. The primary outcome was the presence of pulmonary fibrosis on a CT scan 3 months after discharge; the fibrosis risk was estimated by a multiple logistic regression. The mean patient age was 55.03 ± 12.32 (range 27–85) years; 65 (66.3%) were men and 33 (33.7%) were women. The age, Charlson Comorbidity Index, lactate dehydrogenase level, aspartate aminotransferase level, and Krebs von den Lungen-6 level were significantly higher and the albumin level and the saturation of the peripheral oxygen/fraction of inspired oxygen (SpO2/FiO2) ratio were significantly lower in the fibrosis group than in the non-fibrosis group; the need for initial oxygen support was also greater in the fibrosis group. An older age (adjusted odds ratio (AOR) 1.12; 95% confidence interval (CI) 1.03–1.21) and a lower initial SpO2/FiO2 ratio (AOR 7.17; 95% CI 1.72–29.91) were significant independent risk factors for pulmonary fibrosis after COVID-19 pneumonia. An older age and a low initial SpO2/FiO2 ratio were crucial in predicting pulmonary fibrosis after COVID-19 pneumonia. Full article
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13 pages, 1099 KiB  
Article
Lower Levels of ABO Anti-A and Anti-B of IgM, IgG and IgA Isotypes in the Serum but Not the Saliva of COVID-19 Convalescents
by Eva M. Matzhold, Günther F. Körmöczi, Chiara Banfi, Marlies Schönbacher, Camilla Drexler-Helmberg, Ivo Steinmetz, Andrea Berghold, Peter Schlenke, Gabriel E. Wagner, Anja Stoisser, Barbara Kleinhappl, Wolfgang R. Mayr and Thomas Wagner
J. Clin. Med. 2022, 11(15), 4513; https://doi.org/10.3390/jcm11154513 - 2 Aug 2022
Cited by 1 | Viewed by 2594
Abstract
Individuals with ABO type O, naturally possessing anti-A and anti-B antibodies in their serum, are underrepresented among patients infected with SARS-CoV-2 compared with healthy controls. The ABO antibodies might play a role in the viral transmission. Therefore, we aimed to quantify anti-A/anti-B, including [...] Read more.
Individuals with ABO type O, naturally possessing anti-A and anti-B antibodies in their serum, are underrepresented among patients infected with SARS-CoV-2 compared with healthy controls. The ABO antibodies might play a role in the viral transmission. Therefore, we aimed to quantify anti-A/anti-B, including their subclasses IgM, IgG and IgA, in the serum and saliva of Caucasians (n = 187) after mild COVID-19 to compare them with individuals who had never been infected with SARS-CoV-2. Two samples were collected within two months after the diagnosis (median days: 44) and two months later. ABO antibodies were determined by flow cytometry. Additionally, total IgA in saliva and antibodies specific to SARS-CoV-2 were tested by ELISA. COVID-19 convalescents had significantly lower levels of anti-A/anti-B IgM, IgG and IgA in their serum than control subjects (p < 0.001). Interestingly, no significant differences were observed in saliva. ABO antibody levels remained stable over the period considered. No relation of ABO to the level of SARS-CoV-2-specific antibodies was observed. Total IgA was lower in convalescents than in controls (p = 0.038). Whereas ABO antibodies in the saliva may not contribute to the pathogenesis of COVID-19, individual pre-existing high serum concentrations of anti-A/anti-B may have a protective effect against SARS-CoV-2 infection. Full article
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20 pages, 1857 KiB  
Article
Mathematical Modeling to Predict COVID-19 Infection and Vaccination Trends
by Bogdan Doroftei, Ovidiu-Dumitru Ilie, Nicoleta Anton, Sergiu-Ioan Timofte and Ciprian Ilea
J. Clin. Med. 2022, 11(6), 1737; https://doi.org/10.3390/jcm11061737 - 21 Mar 2022
Cited by 1 | Viewed by 2199
Abstract
Background: COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 placed the health systems around the entire world in a battle against the clock. While most of the existing studies aimed at forecasting the infections trends, our study focuses on vaccination trend(s). [...] Read more.
Background: COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 placed the health systems around the entire world in a battle against the clock. While most of the existing studies aimed at forecasting the infections trends, our study focuses on vaccination trend(s). Material and methods: Based on these considerations, we used standard analyses and ARIMA modeling to predict possible scenarios in Romania, the second-lowest country regarding vaccinations from the entire European Union. Results: With approximately 16 million doses of vaccine against COVID-19 administered, 7,791,250 individuals had completed the vaccination scheme. From the total, 5,058,908 choose Pfizer–BioNTech, 399,327 Moderna, 419,037 AstraZeneca, and 1,913,978 Johnson & Johnson. With a cumulative 2147 local and 17,542 general adverse reactions, the most numerous were reported in recipients of Pfizer–BioNTech (1581 vs. 8451), followed by AstraZeneca (138 vs. 6033), Moderna (332 vs. 1936), and Johnson & Johnson (96 vs. 1122). On three distinct occasions have been reported >50,000 individuals who received the first or second dose of a vaccine and >30,000 of a booster dose in a single day. Due to high reactogenicity in case of AZD1222, and time of launching between the Pfizer–BioNTech and Moderna vaccine could be explained differences in terms doses administered. Furthermore, ARIMA(1,1,0), ARIMA(1,1,1), ARIMA(0,2,0), ARIMA(2,1,0), ARIMA(1,2,2), ARI-MA(2,2,2), ARIMA(0,2,2), ARIMA(2,2,2), ARIMA(1,1,2), ARIMA(2,2,2), ARIMA(2,1,1), ARIMA(2,2,1), and ARIMA (2,0,2) for all twelve months and in total fitted the best models. These were regarded according to the lowest MAPE, p-value (p < 0.05, p < 0.01, and p < 0.001) and through the Ljung–Box test (p < 0.05, p < 0.01, and p < 0.001) for autocorrelations. Conclusions: Statistical modeling and mathematical analyses are suitable not only for forecasting the infection trends but the course of a vaccination rate as well. Full article
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11 pages, 961 KiB  
Article
Activation of the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients with SARS-CoV-2 Infection Could Contribute to COVID-19 Hypofibrinolytic State and Disease Severity Prognosis
by Karen Claesen, Yani Sim, An Bracke, Michelle De bruyn, Emilie De Hert, Gwendolyn Vliegen, An Hotterbeekx, Alexandra Vujkovic, Lida van Petersen, Fien H. R. De Winter, Isabel Brosius, Caroline Theunissen, Sabrina van Ierssel, Maartje van Frankenhuijsen, Erika Vlieghe, Koen Vercauteren, Samir Kumar-Singh, Ingrid De Meester and Dirk Hendriks
J. Clin. Med. 2022, 11(6), 1494; https://doi.org/10.3390/jcm11061494 - 9 Mar 2022
Cited by 3 | Viewed by 2351
Abstract
Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation [...] Read more.
Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection. Full article
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10 pages, 465 KiB  
Article
Real-World Efficacy of Regdanvimab on Clinical Outcomes in Patients with Mild to Moderate COVID-19
by Taeyun Kim, Dong-Hyun Joo, Seung Woo Lee, Jaejun Lee, Sang Jin Lee and Jihun Kang
J. Clin. Med. 2022, 11(5), 1412; https://doi.org/10.3390/jcm11051412 - 4 Mar 2022
Cited by 9 | Viewed by 2372
Abstract
Background: This study aims to evaluate the real-world effectiveness of regdanvimab on clinical outcomes in patients with mild to moderate coronavirus disease 2019 (COVID-19). Methods: This retrospective observational study included 152 patients (89 received regdanvimab and 63 did not) diagnosed with mild to [...] Read more.
Background: This study aims to evaluate the real-world effectiveness of regdanvimab on clinical outcomes in patients with mild to moderate coronavirus disease 2019 (COVID-19). Methods: This retrospective observational study included 152 patients (89 received regdanvimab and 63 did not) diagnosed with mild to moderate COVID-19 between August 2021 and October 2021 and admitted to Armed Forces Goyang Hospital. We collected information on the use of regdanvimab, remdesivir, dexamethasone, and supplemental oxygen; symptom severity score (SSS); and laboratory test results. A linear mixed-effects model was used to test the effectiveness of regdanvimab usage on SSS and the results of laboratory tests. A multivariate logistic regression model was used to calculate the odds ratio (OR) for additional therapeutic options, such as remdesivir, dexamethasone, and supplemental oxygen. Results: The patients who received regdanvimab were older, showed a higher rate of vaccination, and had a higher Charlson comorbidity index, initial body temperature, and percentages of pneumonia at admission. The use of regdanvimab showed no interactive effects on the SSS and laboratory findings. Older age, male sex, obesity, high initial body temperature, and the presence of pneumonia at admission were associated with increased ORs for the use of these additional treatments. The use of regdanvimab reduced the probability of requiring additional therapies such as remdesivir, dexamethasone, and oxygen supplementation by 90.3% (95% confidence interval (CI), 60.3–97.6), 85.8% (95% CI, 34.2–96.9), and 89.8% (95% CI, 48.3–98), respectively. Conclusions: Regdanvimab usage was well tolerated and was associated with a decreased probability of requiring remdesivir, dexamethasone, and oxygen therapy. However, changes in SSS were not significantly different by the drug usage. Full article
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11 pages, 991 KiB  
Article
Using the NYHA Classification as Forecasting Tool for Hospital Readmission and Mortality in Heart Failure Patients with COVID-19
by Ioana Mihaela Citu, Cosmin Citu, Florin Gorun, Radu Neamtu, Andrei Motoc, Bogdan Burlea, Ovidiu Rosca, Felix Bratosin, Samer Hosin, Diana Manolescu, Raul Patrascu and Oana Maria Gorun
J. Clin. Med. 2022, 11(5), 1382; https://doi.org/10.3390/jcm11051382 - 2 Mar 2022
Cited by 19 | Viewed by 2918
Abstract
During the COVID-19 pandemic, it was observed that patients with heart disease are more likely to be hospitalized and develop severe COVID-19. Cardiac disease takes the top position among patient comorbidities, heart failure (HF) prevalence reaching almost 5% in the general population older [...] Read more.
During the COVID-19 pandemic, it was observed that patients with heart disease are more likely to be hospitalized and develop severe COVID-19. Cardiac disease takes the top position among patient comorbidities, heart failure (HF) prevalence reaching almost 5% in the general population older than 35 years in Romania. This retrospective study aimed to determine the potential use of the NYHA classification for HF in hospitalized patients with COVID-19 as prognostic tool for in-hospital mortality, length of hospitalization, and probability of rehospitalization for HF decompensation. We observed that patients with advanced HF had a history of significantly more comorbid conditions that are associated with worse disease outcomes than the rest of patients classified as NYHA I and II. However, regardless of existing diseases, NYHA III, and, especially, NYHA IV, patients were at greatest risk for mortality following SARS-CoV-2 infection. They required significantly longer durations of hospitalization, ICU admission for mechanical ventilation, and developed multiple severe complications. NYHA IV patients required a median duration of 20 days of hospitalization, and their in-hospital mortality was as high as 47.8%. Cardiac biomarkers were significantly altered in patients with SARS-CoV-2 and advanced HF. Although the study sample was small, all patients with NYHA IV who recovered from COVID-19 required a rehospitalization in the following month, and 65.2% of the patients at initial presentation died during the next six months. The most significant risk factor for mortality was the development of severe in-hospital complications (OR = 4.38), while ICU admission was the strongest predictor for rehospitalization (OR = 5.19). Our result highlights that HF patients continue to be vulnerable post SARS-CoV-2 infection. Physicians and policymakers should consider this population’s high likelihood of hospital readmissions when making discharge, hospital capacity planning, and post-discharge patient monitoring choices. Full article
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10 pages, 998 KiB  
Review
Severe Thrombocytopenia as a Manifestation of COVID-19 Infection
by Mihaela Mocan, Roxana Mihaela Chiorescu, Andrada Tirnovan, Botond Sandor Buksa and Anca Daniela Farcaș
J. Clin. Med. 2022, 11(4), 1088; https://doi.org/10.3390/jcm11041088 - 18 Feb 2022
Cited by 5 | Viewed by 3954
Abstract
Clinical manifestations of COVID-19 infection can range from an asymptomatic clinical form to acute respiratory distress depending on the virus gateway, viral load, host immunity, and existing comorbidities. Some patients with COVID-19 infection can present hematological changes depending on the patient’s immune response [...] Read more.
Clinical manifestations of COVID-19 infection can range from an asymptomatic clinical form to acute respiratory distress depending on the virus gateway, viral load, host immunity, and existing comorbidities. Some patients with COVID-19 infection can present hematological changes depending on the patient’s immune response and the severity of the infection. We present two different manifestations of thrombotic disorders related to COVID-19: one severe form of immune thrombocytopenia in a young woman with no comorbidities and a severe form of thrombocytopenia along with disseminated intravascular coagulation and acute urinary obstructive disease. Interestingly, both patients presented no signs of COVID-19 pneumonia. Failure to diagnose thrombocytopenia rapidly may lead to severe complications. Management with immunosuppressive corticosteroids in high doses should carefully balance the risk of bleeding versus deterioration due to infection. Full article
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14 pages, 6173 KiB  
Article
Lymphopenia as a Predictor for Adverse Clinical Outcomes in Hospitalized Patients with COVID-19: A Single Center Retrospective Study of 4485 Cases
by Jianli Niu, Candice Sareli, Daniel Mayer, Alvaro Visbal and Aharon Sareli
J. Clin. Med. 2022, 11(3), 700; https://doi.org/10.3390/jcm11030700 - 28 Jan 2022
Cited by 21 | Viewed by 3404
Abstract
Lymphopenia is commonly present in patients with COVID-19. We sought to determine if lymphopenia on admission predicts COVID-19 clinical outcomes. A retrospective chart review was performed on 4485 patients with laboratory-confirmed COVID-19, who were admitted to the hospital. Of those, 2409 (57.3%) patients [...] Read more.
Lymphopenia is commonly present in patients with COVID-19. We sought to determine if lymphopenia on admission predicts COVID-19 clinical outcomes. A retrospective chart review was performed on 4485 patients with laboratory-confirmed COVID-19, who were admitted to the hospital. Of those, 2409 (57.3%) patients presented with lymphopenia (absolute lymphocyte count < 1.1 × 109/L) on admission, and had higher incidences of ICU admission (17.9% versus 9.5%, p < 0.001), invasive mechanical ventilation (14.4% versus 6.5%, p < 0.001), dialysis (3.4% versus 1.8%, p < 0.001) and in-hospital mortality (16.6% versus 6.6%, p < 0.001), with multivariable-adjusted odds ratios of 1.86 (95% confidence interval [CI], 1.55–2.25), 2.09 (95% CI, 1.69–2.59), 1.77 (95% CI, 1.19–2.68), and 2.19 (95% CI 1.76–2.72) for the corresponding outcomes, respectively, compared to those without lymphopenia. The restricted cubic spline models showed a non-linear relationship between lymphocyte count and adverse outcomes, with an increase in the risk of adverse outcomes for lower lymphocyte counts in patients with lymphopenia. The predictive powers of lymphopenia, expressed as areas under the receiver operating characteristic curves, were 0.68, 0.69, 0.78, and 0.79 for the corresponding adverse outcomes, respectively, after incorporating age, gender, race, and comorbidities. In conclusion, lymphopenia is a useful metric in prognosticating outcomes in hospitalized COVID-19 patients. Full article
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9 pages, 268 KiB  
Review
Are Multiple Chemosensory Systems Accountable for COVID-19 Outcome?
by Antonio Caretta and Carla Mucignat-Caretta
J. Clin. Med. 2021, 10(23), 5601; https://doi.org/10.3390/jcm10235601 - 28 Nov 2021
Cited by 3 | Viewed by 2307
Abstract
Chemosensory systems (olfaction, taste, trigeminus nerve, solitary chemoreceptor cells, neuroendocrine pulmonary cells, and carotid body, etc.) detect molecules outside or inside our body and may share common molecular markers. In addition to the impairment of taste and olfaction, the detection of the internal [...] Read more.
Chemosensory systems (olfaction, taste, trigeminus nerve, solitary chemoreceptor cells, neuroendocrine pulmonary cells, and carotid body, etc.) detect molecules outside or inside our body and may share common molecular markers. In addition to the impairment of taste and olfaction, the detection of the internal chemical environment may also be incapacitated by COVID-19. If this is the case, different consequences can be expected. (1) In some patients, hypoxia does not trigger distressing dyspnea (“silent” hypoxia): Long-term follow-up may determine whether silent hypoxia is related to malfunctioning of carotid body chemoreceptors. Moreover, taste/olfaction and oxygen chemoreceptors may be hit simultaneously: Testing olfaction, taste, and oxygen chemoreceptor functions in the early stages of COVID-19 allows one to unravel their connections and trace the recovery path. (2) Solitary chemosensory cells are also involved in the regulation of the innate mucosal immune response: If these cells are affected in some COVID-19 patients, the mucosal innate immune response would be dysregulated, opening one up to massive infection, thus explaining why COVID-19 has lethal consequences in some patients. Similar to taste and olfaction, oxygen chemosensory function can be easily tested with a non-invasive procedure in humans, while functional tests for solitary chemosensory or pulmonary neuroendocrine cells are not available, and autoptic investigation is required to ascertain their involvement. Full article
11 pages, 759 KiB  
Article
Heart Rate in Patients with SARS-CoV-2 Infection: Prevalence of High Values at Discharge and Relationship with Disease Severity
by Alessandro Maloberti, Nicola Ughi, Davide Paolo Bernasconi, Paola Rebora, Iside Cartella, Enzo Grasso, Deborah Lenoci, Francesca Del Gaudio, Michela Algeri, Sara Scarpellini, Enrico Perna, Alessandro Verde, Caterina Santolamazza, Francesco Vicari, Maria Frigerio, Antonia Alberti, Maria Grazia Valsecchi, Claudio Rossetti, Oscar Massimiliano Epis, Cristina Giannattasio and on the behalf of the Niguarda COVID-19 Working Groupadd Show full author list remove Hide full author list
J. Clin. Med. 2021, 10(23), 5590; https://doi.org/10.3390/jcm10235590 - 28 Nov 2021
Cited by 14 | Viewed by 2210
Abstract
The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a [...] Read more.
The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = β = 0.17 per bpm, 95% CI 0.11; 0.22, p < 0.001), haemoglobin (β = −0.64 per g/dL, 95% CI −1.19; −0.09, p = 0.023) and severe disease (β = 8.42, 95% CI 5.39; 11.45, p < 0.001). High HR at discharge in COVID-19 patients is not such a frequent consequence, but when it occurs it seems strongly related to a severe course of the disease. Full article
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12 pages, 1313 KiB  
Article
Lymphocytopenia and Anti-CD38 Directed Treatment Impact the Serological SARS-CoV-2 Response after Prime Boost Vaccination in Patients with Multiple Myeloma
by Susanne Ghandili, Martin Schönlein, Christian Wiessner, Heiko Becher, Marc Lütgehetmann, Thomas Theo Brehm, Julian Schulze zur Wiesch, Carsten Bokemeyer, Marianne Sinn, Katja C. Weisel and Lisa B. Leypoldt
J. Clin. Med. 2021, 10(23), 5499; https://doi.org/10.3390/jcm10235499 - 24 Nov 2021
Cited by 7 | Viewed by 2128
Abstract
Even though several SARS-CoV-2 vaccines have shown high effectiveness in the prevention of COVID-19 in healthy subjects, vaccination response in patients with plasma-cell-related disorders (PCD) remains widely unknown. Here, we report on an analysis describing the serological response after prime-boost SARS-CoV-2 vaccination in [...] Read more.
Even though several SARS-CoV-2 vaccines have shown high effectiveness in the prevention of COVID-19 in healthy subjects, vaccination response in patients with plasma-cell-related disorders (PCD) remains widely unknown. Here, we report on an analysis describing the serological response after prime-boost SARS-CoV-2 vaccination in PCD patients, as compared to a healthy control group, and on possible influencing factors of serological responses. Blood samples were analyzed for the presence of quantitative anti-SARS-CoV-2 spike RBD Ig. A total of 82 patients were included; 67 received mRNA-, eight vector-based and four heterologous vaccinations. SARS-CoV-2 antibody titers (SP-AbT) were assessed in a mean of 23 days (SD ± 11 days) after the first and in a mean 21 days (SD ± 9) after prime-boost vaccination. A positive SP-AbT was detected in 31.9% of PCD patients after the first vaccination, and in 88.9% (44/49) after prime-boost vaccination, which was significantly less likely than that in the control group (100%, 78/78) (p = 0.008). Furthermore, we have been able to validate our previously suggested threshold of 30 CD19+ B lymphocytes/µL as being predictive for SP-AbT development. Despite anti-CD38 directed therapy, quadruplet treatment, higher age and missing deep remission, which correlated negatively with SP-AbT appearance, SP-AbT formation is possible in a majority of myeloma patients after prime-boost vaccination. Full article
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11 pages, 1320 KiB  
Brief Report
Long-Term Symptoms among Hospitalized COVID-19 Patients 48 Weeks after Discharge—A Prospective Cohort Study
by Martin Mølhave, Steffen Leth, Jesper Damsgaard Gunst, Søren Jensen-Fangel, Lars Østergaard, Christian Wejse and Jane Agergaard
J. Clin. Med. 2021, 10(22), 5298; https://doi.org/10.3390/jcm10225298 - 15 Nov 2021
Cited by 9 | Viewed by 1682
Abstract
Follow-up studies of COVID-19 survivors have been performed to characterize persistence of long-term symptoms, but data are scarce on one year of follow-up. This study provides data from 48 weeks of follow-up after discharge. All patients discharged from the Department of Infectious Diseases [...] Read more.
Follow-up studies of COVID-19 survivors have been performed to characterize persistence of long-term symptoms, but data are scarce on one year of follow-up. This study provides data from 48 weeks of follow-up after discharge. All patients discharged from the Department of Infectious Diseases at Aarhus University Hospital, Denmark between 1 March and 1 July 2020 were followed for 48 weeks. In total, 45 of 66 eligible patients were interviewed after 48 weeks. The median age was 57 (IQR 51–70) years, the majority were female (53%) and Caucasian (87%). Median BMI was 28.1 (IQR 24.8–32.6) kg/m2. One or more comorbidities were registered among 62% of the patients. In total, 39 out of 45 (87%) interviewed patients reported persistence of at least one symptom 48 weeks after hospitalization with COVID-19. Most frequently reported symptoms were fatigue, dyspnea, and concentration difficulties. This study provides new long-term data following COVID-19, contributing to the accumulating data of COVID-19 sequelae. Many patients suffer long-term sequelae and further research is urgently needed to gain further knowledge of the duration and therapeutic options. Full article
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17 pages, 3271 KiB  
Article
Long-Term SARS-CoV-2 Specific Immunity Is Affected by the Severity of Initial COVID-19 and Patient Age
by Margarethe Konik, Monika Lindemann, Markus Zettler, Lara Meller, Sebastian Dolff, Vera Rebmann, Peter A. Horn, Ulf Dittmer, Adalbert Krawczyk, Leonie Schipper, Mirko Trilling, Olympia Evdoxia Anastasiou, Sina Schwarzkopf, Laura Thümmler, Christian Taube, Christoph Schöbel, Thorsten Brenner, Eva-Maria Skoda, Benjamin Wilde, Anja Gäckler, Oliver Witzke and Hana Rohnadd Show full author list remove Hide full author list
J. Clin. Med. 2021, 10(19), 4606; https://doi.org/10.3390/jcm10194606 - 8 Oct 2021
Cited by 9 | Viewed by 2501
Abstract
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. [...] Read more.
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients’ humoral immune responses to Spike (S) protein over the long-term, whereas the patients’ age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity. Full article
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13 pages, 775 KiB  
Review
The Impact of SARS-CoV-2 Infection on Fertility and Female and Male Reproductive Systems
by Agnieszka Markiewicz-Gospodarek, Paulina Wdowiak, Marcin Czeczelewski, Alicja Forma, Jolanta Flieger, Jacek Januszewski, Elżbieta Radzikowska-Büchner and Jacek Baj
J. Clin. Med. 2021, 10(19), 4520; https://doi.org/10.3390/jcm10194520 - 29 Sep 2021
Cited by 10 | Viewed by 3200
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a huge challenge for contemporary healthcare systems. Apart from widely reported acute respiratory distress syndrome (ARDS), the virus affects many other systems inducing a vast number of symptoms such as gastrointestinal, neurological, dermatological, [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a huge challenge for contemporary healthcare systems. Apart from widely reported acute respiratory distress syndrome (ARDS), the virus affects many other systems inducing a vast number of symptoms such as gastrointestinal, neurological, dermatological, cardiovascular, and many more. Currently it has also been hypothesized that the virus might affect female and male reproductive systems; SARS-CoV-2 infection could also have a role in potential disturbances to human fertility. In this article, we aimed to review the latest literature regarding the potential effects of SARS-CoV-2 infection on female and male reproductive systems as well as fertility, in general. Full article
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13 pages, 725 KiB  
Article
Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms
by Tihamer Molnar, Reka Varnai, Daniel Schranz, Laszlo Zavori, Zoltan Peterfi, David Sipos, Margit Tőkés-Füzesi, Zsolt Illes, Andras Buki and Peter Csecsei
J. Clin. Med. 2021, 10(19), 4337; https://doi.org/10.3390/jcm10194337 - 23 Sep 2021
Cited by 17 | Viewed by 4054
Abstract
Background: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies. Methods: Fatigue and [...] Read more.
Background: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies. Methods: Fatigue and memory impairment were assessed in a total of 101 post-COVID subjects using the Chalder fatigue scale (CFQ-11) and a visual analogue scale. Using the bimodal scoring system generated from CFQ-11, a score ≥4 was defined as severe fatigue. Serum anti-SARS-CoV-2 spike (anti-S-Ig) and nucleocapsid (anti-NC-Ig) antibodies were examined at two time points: 4–12 weeks after onset of symptoms, and beyond 12 weeks. Results: The serum level of anti-S-Ig was significantly higher in patients with non-severe fatigue compared to those with severe fatigue at 4–12 weeks (p = 0.006) and beyond 12 weeks (p = 0.016). The serum level of anti-NC-Ig remained high in patients with non-severe fatigue at both time points. In contrast, anti-NC-Ig decreased significantly in severe fatigue cases regardless of the elapsed time (4–12 weeks: p = 0.024; beyond 12 weeks: p = 0.005). The incidence of memory impairment was significantly correlated with lower anti-S-Ig levels (−0.359, p < 0.001). Conclusion: The systemic immune response reflected by antibodies to SARS-CoV-2 is strongly correlated with the severity of post-COVID fatigue. Full article
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11 pages, 944 KiB  
Article
Role of Serum E-Selectin as a Biomarker of Infection Severity in Coronavirus Disease 2019
by Alessandra Oliva, Emanuele Rando, Dania Al Ismail, Massimiliano De Angelis, Francesca Cancelli, Maria Claudia Miele, Raissa Aronica, Vera Mauro, Federica Di Timoteo, Lorenzo Loffredo and Claudio M. Mastroianni
J. Clin. Med. 2021, 10(17), 4018; https://doi.org/10.3390/jcm10174018 - 6 Sep 2021
Cited by 13 | Viewed by 2270
Abstract
Introduction: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients [...] Read more.
Introduction: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients and those with or without thrombosis. Methods: A single-center study of patients with COVID-19 hospitalized at Policlinico Umberto I (Rome) from March to May 2020 was performed. Simple and multiple logistic regression models were developed. Results: One hundred patients were included, with a median age (IQR) of 65 years (58–78). Twenty-nine (29%) were admitted to ICU, twenty-eight (28%) died and nineteen (19%) had a thrombotic event. The median value (IQR) of sE-selectin was 26.1 ng/mL (18.1–35). sE-selectin values did not differ between deceased and survivors (p = 0.06) and among patients with or without a thrombotic event (p = 0.22). Compared with patients who did not receive ICU treatments, patients requiring ICU care had higher levels of sE-selectin (36.6 vs. 24.1 ng/mL; p < 0.001). In the multiple logistic regression model, sE-selectin levels > 33 ng/mL, PaO2/FiO2 < 200 and PaO2/FiO2 200–300 were significantly associated with an increased risk of ICU admission. sE-selectin values significantly correlated with a neutrophil count (R = 0.32 (p = 0.001)) and the number of days from the symptoms onset to hospitalization (R = 0.28 (p = 0.004)). Conclusions: sE-selectin levels are predictive of ICU admission in COVID-19 patients. Since data on the relation between sE-selectin and COVID-19 are scarce, this study aims to contribute toward the comprehension of the pathogenic aspects of COVID-19 disease, giving a possible clinical marker able to predict its severity. Full article
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9 pages, 1421 KiB  
Article
Susceptibility of β-Thalassemia Heterozygotes to COVID-19
by Sotirios Sotiriou, Athina A. Samara, Dimitra Vamvakopoulou, Konstantinos-Odysseas Vamvakopoulos, Andreas Sidiropoulos, Nikolaos Vamvakopoulos, Michel B. Janho, Konstantinos I. Gourgoulianis and Styllianos Boutlas
J. Clin. Med. 2021, 10(16), 3645; https://doi.org/10.3390/jcm10163645 - 18 Aug 2021
Cited by 9 | Viewed by 3833
Abstract
Background: β-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomedical priority. Methods: We studied 255 positive COVID-19 participants unvaccinated against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), consecutively [...] Read more.
Background: β-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomedical priority. Methods: We studied 255 positive COVID-19 participants unvaccinated against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), consecutively recruited during the last trimester of 2020. Patient characteristics including age, sex, current smoking status, atrial fibrillation, chronic respiratory disease, coronary disease, diabetes, neoplasia, hyperlipidemia, hypertension, and β-thalassemia heterozygosity were assessed for COVID-19 severity, length of hospitalization, intensive care unit (ICU) admission and mortality from COVID-19. Results: We assessed patient characteristics associated with clinical symptoms, ICU admission, and mortality from COVID-19. In multivariate analysis, severe-critical COVID-19 was strongly associated with male sex (p = 0.023), increased age (p < 0.001), and β-thalassemia heterozygosity (p = 0.002, OR = 2.89). Regarding the requirement for ICU care, in multivariate analysis there was a statistically significant association with hypertension (p = 0.001, OR = 5.12), while β-thalassemia heterozygosity had no effect (p = 0.508, OR = 1.33). Mortality was linked to male sex (p = 0.036, OR = 2.09), increased age (p < 0.001) and β-thalassemia heterozygosity (p = 0.010, OR = 2.79) in multivariate analysis. It is worth noting that hyperlipidemia reduced mortality from COVID-19 (p = 0.008, OR = 0.38). No statistically significant association of current smoking status with patient characteristics studied was observed. Conclusions: Our pilot observations indicate enhanced mortality of β-thalassemia heterozygotes from COVID-19. Full article
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26 pages, 7154 KiB  
Article
Weighted Gene Co-Expression Network Analysis Combined with Machine Learning Validation to Identify Key Modules and Hub Genes Associated with SARS-CoV-2 Infection
by Hassan Karami, Afshin Derakhshani, Mohammad Ghasemigol, Mohammad Fereidouni, Ebrahim Miri-Moghaddam, Behzad Baradaran, Neda Jalili Tabrizi, Souzan Najafi, Antonio Giovanni Solimando, Leigh M. Marsh, Nicola Silvestris, Simona De Summa, Angelo Virgilio Paradiso, Vito Racanelli and Hossein Safarpour
J. Clin. Med. 2021, 10(16), 3567; https://doi.org/10.3390/jcm10163567 - 13 Aug 2021
Cited by 28 | Viewed by 4593
Abstract
The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous loss of lives. Various clinical trials of vaccines and drugs are being conducted worldwide; nevertheless, as of today, no effective drug exists for COVID-19. The identification of key genes and pathways in this disease [...] Read more.
The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous loss of lives. Various clinical trials of vaccines and drugs are being conducted worldwide; nevertheless, as of today, no effective drug exists for COVID-19. The identification of key genes and pathways in this disease may lead to finding potential drug targets and biomarkers. Here, we applied weighted gene co-expression network analysis and LIME as an explainable artificial intelligence algorithm to comprehensively characterize transcriptional changes in bronchial epithelium cells (primary human lung epithelium (NHBE) and transformed lung alveolar (A549) cells) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our study detected a network that significantly correlated to the pathogenicity of COVID-19 infection based on identified hub genes in each cell line separately. The novel hub gene signature that was detected in our study, including PGLYRP4 and HEPHL1, may shed light on the pathogenesis of COVID-19, holding promise for future prognostic and therapeutic approaches. The enrichment analysis of hub genes showed that the most relevant biological process and KEGG pathways were the type I interferon signaling pathway, IL-17 signaling pathway, cytokine-mediated signaling pathway, and defense response to virus categories, all of which play significant roles in restricting viral infection. Moreover, according to the drug–target network, we identified 17 novel FDA-approved candidate drugs, which could potentially be used to treat COVID-19 patients through the regulation of four hub genes of the co-expression network. In conclusion, the aforementioned hub genes might play potential roles in translational medicine and might become promising therapeutic targets. Further in vitro and in vivo experimental studies are needed to evaluate the role of these hub genes in COVID-19. Full article
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12 pages, 674 KiB  
Article
Ruling Out Coronavirus Disease 2019 in Patients with Pneumonia: The Role of Blood Cell Count and Lung Ultrasound
by Gianni Biolo, Nicola Fiotti, Franco Cominotto, Filippo Giorgio Di Girolamo, Emiliano Panizon, Nicola Altamura, Chiara Casarsa, Alessandro Pipoli, Mauro Giordano, Lucio Torelli, Filippo Mearelli and Pierandrea Vinci
J. Clin. Med. 2021, 10(16), 3481; https://doi.org/10.3390/jcm10163481 - 6 Aug 2021
Cited by 3 | Viewed by 1788
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a distinctive blood leucocyte pattern and B-lines on lung ultrasound (LUS) as marker of alveolar-interstitial syndrome. We aimed to evaluate the accuracy of blood leucocyte count alone or in combination with LUS for COVID-19 diagnosis. We [...] Read more.
Coronavirus disease 2019 (COVID-19) is characterized by a distinctive blood leucocyte pattern and B-lines on lung ultrasound (LUS) as marker of alveolar-interstitial syndrome. We aimed to evaluate the accuracy of blood leucocyte count alone or in combination with LUS for COVID-19 diagnosis. We retrospectively enrolled consecutive patients diagnosed with community acquired pneumonia (CAP) at hospital admission to derive and validate cutoff values for blood cell count that could be predictive of COVID-19 before confirmation by the nucleic acid amplification test (NAAT). Cutoff values, generated and confirmed in inception (41/115, positive/negative patients) and validation (100/180, positive/negative patients) cohorts, were ≤17 and ≤10 cells/mm3 for basophils and eosinophils, respectively. Basophils and/or eosinophils below cutoff were associated with sensitivity of 98% (95%CI, 94–100) and negative likelihood ratio of 0.04 (95%CI, 0.01–0.11). In a subgroup of 265 subjects, the sensitivity of B-line on LUS was 15% lower (p < 0.001) than that of basophils and/or eosinophils below cutoff. The combination of B-lines with basophils and eosinophils below cutoff was associated with a moderate increase of the positive likelihood ratio: 5.0 (95%CI, 3.2–7.7). In conclusion, basophil and eosinophil counts above the generated cutoff virtually rule out COVID-19 in patients with CAP. Our findings can help optimize patient triage pending the NAAT results. Full article
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26 pages, 2187 KiB  
Review
SARS-CoV-2 and Acute Cerebrovascular Events: An Overview
by Mehdi Ghasemi, Raffaella Pizzolato Umeton, Kiandokht Keyhanian, Babak Mohit, Nasrin Rahimian, Niloofarsadaat Eshaghhosseiny and Vahid Davoudi
J. Clin. Med. 2021, 10(15), 3349; https://doi.org/10.3390/jcm10153349 - 29 Jul 2021
Cited by 12 | Viewed by 3333
Abstract
Since the coronavirus disease 2019 (COVID-19) pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, accumulating evidence indicates that SARS-CoV-2 infection may be associated with various neurological manifestations, including acute cerebrovascular events (i.e., stroke and cerebral venous thrombosis). These events can [...] Read more.
Since the coronavirus disease 2019 (COVID-19) pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, accumulating evidence indicates that SARS-CoV-2 infection may be associated with various neurological manifestations, including acute cerebrovascular events (i.e., stroke and cerebral venous thrombosis). These events can occur prior to, during and even after the onset of COVID-19’s general symptoms. Although the mechanisms underlying the cerebrovascular complications in patients with COVID-19 are yet to be fully elucidated, the hypercoagulability state, inflammation and altered angiotensin-converting enzyme 2 (ACE-2) signaling in association with SARS-CoV-2 may play key roles. ACE-2 plays a critical role in preserving heart and brain homeostasis. In this review, we discuss the current state of knowledge of the possible mechanisms underlying the acute cerebrovascular events in patients with COVID-19, and we review the current epidemiological studies and case reports of neurovascular complications in association with SARS-CoV-2, as well as the relevant therapeutic approaches that have been considered worldwide. As the number of published COVID-19 cases with cerebrovascular events is growing, prospective studies would help gather more valuable insights into the pathophysiology of cerebrovascular events, effective therapies, and the factors predicting poor functional outcomes related to such events in COVID-19 patients. Full article
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13 pages, 2864 KiB  
Article
One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms
by Andreas Rank, Athanasia Tzortzini, Elisabeth Kling, Christoph Schmid, Rainer Claus, Eva Löll, Roswitha Burger, Christoph Römmele, Christine Dhillon, Katharina Müller, Philipp Girl, Reinhard Hoffmann, Stefanie Grützner and Kevin M. Dennehy
J. Clin. Med. 2021, 10(15), 3305; https://doi.org/10.3390/jcm10153305 - 27 Jul 2021
Cited by 33 | Viewed by 4607
Abstract
After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including [...] Read more.
After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19. Full article
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29 pages, 477 KiB  
Review
COVID-19 and the Endocrine System: A Comprehensive Review on the Theme
by Giuseppe Lisco, Anna De Tullio, Assunta Stragapede, Antonio Giovanni Solimando, Federica Albanese, Martina Capobianco, Vito Angelo Giagulli, Edoardo Guastamacchia, Giovanni De Pergola, Angelo Vacca, Vito Racanelli and Vincenzo Triggiani
J. Clin. Med. 2021, 10(13), 2920; https://doi.org/10.3390/jcm10132920 - 29 Jun 2021
Cited by 62 | Viewed by 7400
Abstract
Background and aim. The review aimed to summarize advances in the topic of endocrine diseases and coronavirus disease 2019 (COVID-19). Methods. Scientific and institutional websites and databases were searched and data were collected and organized, when plausible, to angle the discussion toward the [...] Read more.
Background and aim. The review aimed to summarize advances in the topic of endocrine diseases and coronavirus disease 2019 (COVID-19). Methods. Scientific and institutional websites and databases were searched and data were collected and organized, when plausible, to angle the discussion toward the following clinical issues. (1) Are patients with COVID-19 at higher risk of developing acute or late-onset endocrine diseases or dysfunction? (2) May the underlying endocrine diseases or dysfunctions be considered risk factors for poor prognosis once the infection has occurred? (3) Are there defined strategies to manage endocrine diseases despite pandemic-related constraints? Herein, the authors considered only relevant and more frequently observed endocrine diseases and disorders related to the hypothalamic-pituitary region, thyroid and parathyroid glands, calcium-phosphorus homeostasis and osteoporosis, adrenal glands, and gonads. Main. Data highlight the basis of some pathophysiological mechanisms and anatomical alterations of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-induced endocrine dysfunctions. Some conditions, such as adrenal insufficiency and cortisol excess, may be risk factors of worse clinical progression once the infection has occurred. These at-risk populations may require adequate education to avoid the SARS-CoV-2 infection and adequately manage medical therapy during the pandemic, even in emergencies. Endocrine disease management underwent a palpable restraint, especially procedures requiring obligate access to healthcare facilities for diagnostic and therapeutic purposes. Strategies of clinical triage to prioritize medical consultations, laboratory, instrumental evaluations, and digital telehealth solutions should be implemented to better deal with this probably long-term situation. Full article
8 pages, 612 KiB  
Review
The Role of Neuropilin-1 (NRP-1) in SARS-CoV-2 Infection: Review
by Monika Gudowska-Sawczuk and Barbara Mroczko
J. Clin. Med. 2021, 10(13), 2772; https://doi.org/10.3390/jcm10132772 - 24 Jun 2021
Cited by 41 | Viewed by 5855
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in 2019, is responsible for the global coronavirus disease 19 (COVID-19) pandemic. The main protein that interacts with the host cell receptor is the Spike-1 (S1) subunit of the coronavirus. This subunit binds with receptors [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in 2019, is responsible for the global coronavirus disease 19 (COVID-19) pandemic. The main protein that interacts with the host cell receptor is the Spike-1 (S1) subunit of the coronavirus. This subunit binds with receptors present on the host cell membrane. It has been identified from several studies that neuropilin-1 (NRP-1) is one of the co-receptors for SARS-CoV-2 entry. Therefore, in this review, we focus on the significance of NRP-1 in SARS-CoV-2 infection. MEDLINE/PubMed database was used for a search of available literature. In the current review, we report that NRP-1 plays many important functions, including angiogenesis, neuronal development, and the regulation of immune responses. Additionally, the presence of this glycoprotein on the host cell membrane significantly augments the infection and spread of SARS-CoV-2. Literature data suggest that NRP-1 facilitates entry of the virus into the central nervous system through the olfactory epithelium of the nasal cavity. Moreover, published findings show that interfering with VEGF-A/NRP-1 using NRP-1 inhibitors may produce an analgesic effect. The review describes an association between NRP-1, SARS-CoV-2 and, inter alia, pathological changes in the retina. Based on the published findings, we suggest that NRP-1 is a very important mediator implicated in, inter alia, neurological manifestations of SARS-CoV-2 infection. Additionally, it appears that the use of NRP-1 inhibitors is a promising therapeutic strategy for the treatment of SARS-CoV-2 infection. Full article
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11 pages, 1029 KiB  
Article
Clinical Implications of Neurological Comorbidities and Complications in ICU Patients with COVID-19
by Jaeseok Park, Yong-Shik Kwon, Hyun-Ah Kim, Doo-Hyuk Kwon, Jihye Hwang, Seong-Hwa Jang, Hyungjong Park, Sung-Il Sohn, Huimahn Alex Choi and Jeong-Ho Hong
J. Clin. Med. 2021, 10(11), 2281; https://doi.org/10.3390/jcm10112281 - 25 May 2021
Cited by 8 | Viewed by 2226
Abstract
Clinical implications of neurological problems during intensive care unit (ICU) care for coronavirus disease 2019 (COVID-19) patients are unknown. This study aimed to describe the clinical implications of preexisting neurological comorbidities and new-onset neurological complications in ICU patients with COVID-19. ICU patients who [...] Read more.
Clinical implications of neurological problems during intensive care unit (ICU) care for coronavirus disease 2019 (COVID-19) patients are unknown. This study aimed to describe the clinical implications of preexisting neurological comorbidities and new-onset neurological complications in ICU patients with COVID-19. ICU patients who were isolated and treated for COVID-19 between 19 February 2020 and 3 May 2020, from one tertiary hospital and one government-designated branch hospital were included. Clinical data including previous neurological disorders were extracted from electronic medical records. All neurological complications were evaluated by neurointensivists. Multiple logistic regression analysis was performed to investigate independent factors in ICU mortality. The median age of 52 ICU patients with COVID-19 was 73 years. Nineteen (36.5%) patients had preexisting neurological comorbidities, and new-onset neurological complications occurred in 23 (44.2%) during ICU admission. Patients with preexisting neurological comorbidities required tracheostomy more frequently and more ventilator and ICU days than those without. Patients with new-onset neurological complications experienced more medical complications and had higher ICU severity score and ICU mortality rates. New-onset neurological complications remained an independent factor for ICU mortality. Many COVID-19 patients in the ICU have preexisting neurological comorbidities, making them at a high risk of new-onset neurological complications. Full article
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12 pages, 2310 KiB  
Article
Patient Characteristics and Clinical Course of COVID-19 Patients Treated at a German Tertiary Center during the First and Second Waves in the Year 2020
by Thomas Theo Brehm, Andreas Heyer, Kevin Roedl, Dominik Jarczak, Axel Nierhaus, Michael F Nentwich, Marc van der Meirschen, Alexander Schultze, Martin Christner, Walter Fiedler, Nicolaus Kröger, Tobias B Huber, Hans Klose, Martina Sterneck, Sabine Jordan, Benno Kreuels, Stefan Schmiedel, Marylyn M Addo, Samuel Huber, Ansgar W Lohse, Stefan Kluge and Julian Schulze zur Wieschadd Show full author list remove Hide full author list
J. Clin. Med. 2021, 10(11), 2274; https://doi.org/10.3390/jcm10112274 - 24 May 2021
Cited by 18 | Viewed by 3319
Abstract
In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February–28 July 2020) and second (29 July–31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first [...] Read more.
In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February–28 July 2020) and second (29 July–31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73]; p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4]; p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19]; p < 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54]; p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity. Full article
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17 pages, 2321 KiB  
Review
A State-of-the-Art Survey on Artificial Intelligence to Fight COVID-19
by Md. Mohaimenul Islam, Tahmina Nasrin Poly, Belal Alsinglawi, Ming Chin Lin, Min-Huei Hsu and Yu-Chuan (Jack) Li
J. Clin. Med. 2021, 10(9), 1961; https://doi.org/10.3390/jcm10091961 - 2 May 2021
Cited by 13 | Viewed by 4978
Abstract
Artificial intelligence (AI) has shown immense potential to fight COVID-19 in many ways. This paper focuses primarily on AI’s role in managing COVID-19 using digital images, clinical and laboratory data analysis, and a summary of the most recent articles published last year. We [...] Read more.
Artificial intelligence (AI) has shown immense potential to fight COVID-19 in many ways. This paper focuses primarily on AI’s role in managing COVID-19 using digital images, clinical and laboratory data analysis, and a summary of the most recent articles published last year. We surveyed the use of AI for COVID-19 detection, screening, diagnosis, the progression of severity, mortality, drug repurposing, and other tasks. We started with the technical overview of all models used to fight the COVID-19 pandemic and ended with a brief statement of the current state-of-the-art, limitations, and challenges. Full article
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12 pages, 1347 KiB  
Article
Risk Factors for Mortality in Adult COVID-19 Patients Who Develop Bloodstream Infections Mostly Caused by Antimicrobial-Resistant Organisms: Analysis at a Large Teaching Hospital in Italy
by Brunella Posteraro, Giulia De Angelis, Giulia Menchinelli, Tiziana D’Inzeo, Barbara Fiori, Flavio De Maio, Venere Cortazzo, Maurizio Sanguinetti and Teresa Spanu
J. Clin. Med. 2021, 10(8), 1752; https://doi.org/10.3390/jcm10081752 - 17 Apr 2021
Cited by 13 | Viewed by 2742
Abstract
The aim of this study was to characterize COVID-19 (SARS-CoV-2-infected) patients who develop bloodstream infection (BSI) and to assess risk factors associated with in-hospital mortality. We conducted a retrospective observational study of adult patients admitted for ≥48 h to a large Central Italy [...] Read more.
The aim of this study was to characterize COVID-19 (SARS-CoV-2-infected) patients who develop bloodstream infection (BSI) and to assess risk factors associated with in-hospital mortality. We conducted a retrospective observational study of adult patients admitted for ≥48 h to a large Central Italy hospital for COVID-19 (1 March to 31 May 2020) who had or had not survived at discharge. We included only patients having blood cultures drawn or other inclusion criteria satisfied. Kaplan–Meier survival or Cox regression analyses were performed of 293 COVID-19 patients studied, 46 patients (15.7%) had a hospital-acquired clinically relevant BSI secondary to SARS-CoV-2 infection, accounting for 58 episodes (49 monomicrobial and 9 polymicrobial) in total. Twelve episodes (20.7%) occurred at day 3 of hospital admission. Sixty-nine species were isolated, including Staphylococcus aureus (32.8%), Enterobacterales (20.7%), Enterococcus faecalis (17.2%), Candida (13.8%) and Pseudomonas aeruginosa (10.3%). Of 69 isolates, 27 (39.1%) were multidrug-resistant organisms. Twelve (54.5%) of 22 patients for whom empirical antimicrobial therapy was inappropriate were infected by a multidrug-resistant organism. Of 46 patients, 26 (56.5%) survived and 20 (43.5%) died. Exploring variables for association with in-hospital mortality identified > 75-year age (HR 2.97, 95% CI 1.15–7.68, p = 0.02), septic shock (HR 6.55, 95% CI 2.36–18.23, p < 0.001) and BSI onset ≤ 3 days (HR 4.68, 95% CI 1.40–15.63, p = 0.01) as risk factors independently associated with death. In our hospital, mortality among COVID-19 patients with BSI was high. While continued vigilance against these infections is essential, identification of risk factors for mortality may help to reduce fatal outcomes in patients with COVID-19. Full article
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11 pages, 13470 KiB  
Article
Statin Use Is Associated with a Decreased Risk of Mortality among Patients with COVID-19
by Chieh-Chen Wu, An-Jen Lee, Chun-Hsien Su, Chu-Ya Huang, Md. Mohaimenul Islam and Yung-Ching Weng
J. Clin. Med. 2021, 10(7), 1450; https://doi.org/10.3390/jcm10071450 - 1 Apr 2021
Cited by 13 | Viewed by 3126
Abstract
Background: Recent epidemiological studies remain controversial regarding the association between statin use and reducing the risk of mortality among individuals with COVID-19. Objective: The objective of this study was to clarify the association between statin use and the risk of mortality among patients [...] Read more.
Background: Recent epidemiological studies remain controversial regarding the association between statin use and reducing the risk of mortality among individuals with COVID-19. Objective: The objective of this study was to clarify the association between statin use and the risk of mortality among patients with COVID-19. Methods: We conducted a systematic articles search of online databases (PubMed, EMBASE, Scopus, and Web of Science) between 1 February 2020 and 20 February 2021, with no restriction on language. The following search terms were used: “Statins” and “COVID-19 mortality or COVID19 mortality or SARS-CoV-2 related mortality”. Two authors individually examined all articles and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for study inclusion and exclusion. The overall risk ratio (RRs) with 95% confidence interval (CI) was calculated to show the strength of the association and the heterogeneity among the studies was presented Q and I2 statistic. Results: Twenty-eight studies were assessed for eligibility and 22 studies met the inclusion criteria. Statin use was associated with a significantly decreased risk of mortality among patients with COVID-19 (RR adjusted = 0.64; 95% CI: 0.57–0.72, p < 0.001). Moreover, statin use both before and after the admission was associated with lowering the risk of mortality among the COVID-19 patients (RR adjusted;before = 0.69; 95% CI: 0.56–0.84, p < 0.001 and RR adjusted;after = 0.57; 95% CI: 0.54–0.60, p < 0.001). Conclusion: This comprehensive study showed that statin use is associated with a decreased risk of mortality among individuals with COVID-19. A randomized control trial is needed to confirm and refute the association between them. Full article
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7 pages, 544 KiB  
Article
Spontaneous Pneumomediastinum, Pneumothorax, Pneumopericardium and Subcutaneous Emphysema—Not So Uncommon Complications in Patients with COVID-19 Pulmonary Infection—A Series of Cases
by Talida Georgiana Cut, Cristina Tudoran, Voichita Elena Lazureanu, Adelina Raluca Marinescu, Raluca Dumache and Mariana Tudoran
J. Clin. Med. 2021, 10(7), 1346; https://doi.org/10.3390/jcm10071346 - 24 Mar 2021
Cited by 21 | Viewed by 3555
Abstract
(1) Background: Spontaneous pneumomediastinum (PM), pneumothorax (PT), and pneumopericardium (PP) were recently reported as rare complications in patients with severe COVID-19 pneumonia, and our study aims to follow the evolution of these involvements in 11 cases. The presumed pathophysiological mechanism is air leak [...] Read more.
(1) Background: Spontaneous pneumomediastinum (PM), pneumothorax (PT), and pneumopericardium (PP) were recently reported as rare complications in patients with severe COVID-19 pneumonia, and our study aims to follow the evolution of these involvements in 11 cases. The presumed pathophysiological mechanism is air leak due to extensive diffuse alveolar damage followed by alveolar rupture. (2) Methods: We followed the occurrence of PM, PN, PP, and subcutaneous emphysema (SE) in 1648 patients hospitalized during the second outbreak of COVID-19 (October 2020–January 2021) in the main hospital of infectious diseases of our county and recorded their demographic data, laboratory investigations and clinical evolution. (3) Results: Eleven patients (0.66%) developed PM, with eight of them having associated PT, one PP, and seven SE, in the absence of mechanical ventilation. Eight patients (72.72%) died and only three (27.27%) survived. All subjects were nonsmokers, without known pulmonary pathology or risk factors for such complications. (4) Conclusions: pneumomediastinum, pneumothorax, and pneumopericardium are not so uncommon complications of SARS-CoV2 pneumonia, being observed mostly in male patients with severe forms and associated with prolonged hospitalization and poor prognosis. In some cases, with mild forms and reduced pulmonary injury, the outcome is favorable, not requiring surgical procedures, mechanical ventilation, or intensive care stay. Full article
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9 pages, 1763 KiB  
Article
Arginase 1 (Arg1) as an Up-Regulated Gene in COVID-19 Patients: A Promising Marker in COVID-19 Immunopathy
by Afshin Derakhshani, Nima Hemmat, Zahra Asadzadeh, Moslem Ghaseminia, Mahdi Abdoli Shadbad, Golamreza Jadideslam, Nicola Silvestris, Vito Racanelli and Behzad Baradaran
J. Clin. Med. 2021, 10(5), 1051; https://doi.org/10.3390/jcm10051051 - 4 Mar 2021
Cited by 28 | Viewed by 3464
Abstract
Background: The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic. It is well-established that SARS-CoV-2 infection can lead to dysregulated immune responses. Arginase-1 (Arg1), which has a pivotal role in immune [...] Read more.
Background: The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic. It is well-established that SARS-CoV-2 infection can lead to dysregulated immune responses. Arginase-1 (Arg1), which has a pivotal role in immune cells, can be expressed in most of the myeloid cells, e.g., neutrophils and macrophages. Arg1 has been associated with the suppression of antiviral immune responses. Methods: Whole blood was taken from 21 COVID-19 patients and 21 healthy individuals, and after RNA extraction and complementary DNA (cDNA) synthesis, gene expression of Arg1 was measured by real-time PCR. Results: The qPCR results showed that the expression of Arg1 was significantly increased in COVID-19 patients compared to healthy individuals (p < 0.01). The relative expression analysis demonstrated there were approximately 2.3 times increased Arg1 expression in the whole blood of COVID-19 patients. Furthermore, the receiver operating characteristic (ROC) analysis showed a considerable diagnostic value for Arg1 expression in COVID-19 (p = 0.0002 and AUC = 0.8401). Conclusion: Arg1 might be a promising marker in the pathogenesis of the disease, and it could be a valuable diagnostic tool. Full article
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20 pages, 629 KiB  
Review
The Rheumatology Drugs for COVID-19 Management: Which and When?
by Fabiola Atzeni, Ignazio Francesco Masala, Javier Rodríguez-Carrio, Roberto Ríos-Garcés, Elisabetta Gerratana, Laura La Corte, Manuela Giallanza, Valeria Nucera, Agostino Riva, Gerard Espinosa and Ricard Cervera
J. Clin. Med. 2021, 10(4), 783; https://doi.org/10.3390/jcm10040783 - 16 Feb 2021
Cited by 17 | Viewed by 4330
Abstract
Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor [...] Read more.
Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. ‘Repurposing’ immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients. Full article
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